Although the sympathetic nervous system undoubtedly plays an important role in cardiovascular homeostasis, it has not been shown that sympathetic dysfunction alone can cause hypertension. Accordingly, I propose to test the hypothesis that hypertension results only when sympathetic overactivity is superimposed on other predisposing factors. Whenever technically feasible, experiments will be done on conscious rats to avoid distortion of results by anesthesia. Aside from blood pressure and heart rate, sympathetic nerve activity will also be recorded. Sympathetic vasomotor tone will be increased by chronic electrical stimulation of the hypothalamus or by prolonged exposure to mechanical agitation (vibration) and these procedures will then be combined with changes in salt intake or in renal, adrenocortical, or buffer nerve function. To allow detailed examination of central mechanisms for cardiovascular regulation, a cross-perfused head preparation has been developed in my laboratory. Using this preparation I have obtained evidence indicating that Alpha-adrenergic mechanisms no longer function normally in various forms of experimental hypertension. By providing much needed information on basic derangements in experimental hypertension the proposed studies could improve our understanding of the disease and facilitate development of unempirical and effective therapy.